In psoriasis, would healing, and other skin diseases normal keratinocyte differentiation process is altered and the cells display proliferation and increased motility. This change in cell behavior requires significant remodeling of the actin cytoskeleton. The goal of this study is to obtain new insights regarding the function of the actin cytoskeletal system, and proteins that regulate its function, in keratinocytes. The actin cytoskeleton is a dynamic filamentous network that must alter structure to permit cell proliferation, cell shape change, and cell movement. This network is regulated by calponins. Calponins comprise a family of actin filament-associated proteins that inhibit actin-activated myosin ATPase activity. This, in turn, leads to decreased cell motility and reduced remodeling of the actin cytoskeleton. Protein kinase C (PKC) catalyzed phosphorylation of calponin releases the calponin-dependent inhibition. Three homologous calponin genes have been identified. These encode h1, h2, and acidic calponin isoforms. H2-calponin is expressed in keratinocytes, but its function has not been investigated. We hypothesize that h2-calponin may function to regulate actin-associated filament formation in keratinocytes and modulate keratinocyte proliferation, motility, and differentiation in normal and diseased epidermis. Three specific aims are proposed in this Pilot and Feasibility study: Specific Aim 1: We will study the level of h2-calponin, and h2-calponin subcellular distribution as a function of keratinocyte proliferation rate. Specific Aim 2: We hypothesize that h2-calponin expression is elevated in proliferating keratinocytes to regulate actin-cytoskeleton remodeling during proliferation. We further hypothesize that overexpression of h2-calponin will result in elevated levels of under-phosphorylated h2-calponin and that this will lead to suppression of cell proliferation. To test these hypotheses, we will use vector-mediated gene delivery to study the effect of over- and under-expression of h2-calponin on keratinocyte profliferation. Specific Aim 3: We hypothesize that PKC modulates h2-calponin activity in proliferating karatinocytes. We will investigate the role of PKC-catalyzed phosphorylation of h2-calponin of keratinocyte proliferation and differentiation by over-expressing various PKC isoforms in the presence or absence over-expressed h2-calponin. Parallel experiments will manipulate PKC activity using pharmacologic agents.